Overexpression of CFL1 in gastric cancer and the effects of its silencing by siRNA with a nanoparticle delivery system in the gastric cancer cell line

Abstract

Gastric adenocarcinoma, like other cancers, is a multifactorial genetic disease, and metastasis of cancer cells is one of the main features of this illness. The expression levels of the CFL1 gene have been modulated in this pathway. Using small interfering RNA (siRNA) in the treatment of gastric cancer is considered a hopeful gene therapeutic approach. The present study reported the level of CFL1 genes between tumor and margin and healthy tissue of gastric cancer. Also, the features of a cationic nanoparticle with a polymer coating containing polyacrylic acid and polyethyleneimine that were used in the delivery of CFL1 siRNA, were shown. Then the cytotoxicity, cellular uptake, and gene silencing efficiency of this nanoparticle were evaluated with CFL1siRNA.Method: In this study, the CFL1 gene expression was measured in 40 gastric adenocarcinoma, marginal and 15 healthy biopsy samples by a real-time polymerase chain reaction. Physicochemical characteristics, apoptosis, and inhibition of migration of the delivery of CFL1 siRNA by nanoparticle and lipofectamine were investigated in gastric cancer cells.Result: The CFL1 expression was remarkably increased in gastric cancer tissues in comparison with the marginal samples and normal tissues (p < .05) and the biomarker index for CFL1 was obtained as 0.94, then this gene can be probably used as a biomarker for gastric cancer. After treatment of the AGS cell line by CFL1 siRNA, the CFL1 expression level of mRNA and migration in AGS cells were remarkably suppressed after transfection. Furthermore, the amount of apoptosis increased (p < .05). Conclusion:Our results demonstrated that CFL1 downregulation in AGS cells can interdict cell migration. Finally, our outcomes propose that CFL1 can function as an oncogenic gene in gastric cancer and would be considered as a potential purpose of gene therapy for gastric cancer treatment.

Signaling pathways and therapeutic interventions in gastric cancer

“…Recognition of novel molecular targets has also paved the way for developing gene therapy as a promising molecular alternative in GC treatment, including gene silencing approaches to inactivate oncogenes, replacing defective tumor suppressor genes, introducing suicide genes, genetic immunotherapy, and so forth. The therapeutic potential of genetic approaches has been demonstrated in certain in vitro studies, such as a nanoparticle-delivered siRNA to suppress oncogene CFL1 639 and a CRISPR/Cas9 system-delivered LncRNA PANDAR (promoter of CDKN1A antisense DNA damage activated RNA) to interact with p53 and competitively regulate CDKN1A transcription in GC cell lines. 640 Like drug-based therapies, the major challenge of gene therapy lies in finding a way to circumvent non-responsiveness, which is caused by immunogenic effects after the delivery of genetic material.…”

A domain-based vaccine construct against SARS-CoV-2, the causative agent of COVID-19 pandemic: development of self-amplifying mRNA and peptide vaccines

“…To produce the designed recombinant protein vaccine in a lab setting, a suitable expression host such as microalgae can be used to express the recombinant vaccine with the optimal post-translational modifications. 109,110 In the case of SAMV construct, although both the non-viral delivery systems (e.g., lipid nanoparticles, 111 polymeric nanoparticles, 112 and cell-penetrating peptides 113 ), and in vivo transfection systems (e.g., injection, electroporation, and gene gun) can improve the stability and cellular uptake efficacy, however, the naked SAM vaccine can be taken up as well by significantly antigen-presenting cells without any additional required formulation. 114…”

The combination of positive anti‑WDR1 antibodies with negative anti‑CFL1 antibodies in serum is a poor prognostic factor for patients with esophageal carcinoma

“…Large-scale SEREX screening has already identified numerous antibodies or antigens, such as trophoblast cell surface antigen 2 (3), solute carrier family 2 member 1 (4), striatin 4 (5), LDL receptor related protein associated protein 1 (6), proprotein convertase subtilisin/kexin type 9 (7), cofilin 1 (CFL1) and β-actin (ACTB) (8). CFL1 can depolymerize F-actin in a pH-dependent manner and is also involved in lung, pancreatic, and gastric cancer invasion and metastasis (9)(10)(11).…”